• English
  • 简体中文
Login Register
Current Location: Home > Feedback Help Print

【结 构 式】

【分子编号】50872

【品名】3-(2-[4-[(2,4-difluorophenyl)(hydroxyimino)methyl]-1-piperidinyl]ethyl)-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-one

【CA登记号】

【 分 子 式 】C23H28F2N4O2

【 分 子 量 】430.4978864

【元素组成】C 64.17% H 6.56% F 8.83% N 13.01% O 7.43%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(XIV)

The condensation of piperidine-4-carboxylic acid (VI) with ethyl chloroformate (VII) by means of Na2CO3 in toluene/water gives 1-(ethoxycarbonyl)piperidine-4-carboxylic acid (VIII), which is treated with SOCl2 to yield the corresponding acyl chloride (IX). The Friedel-Crafts condensation of (IX) with refluxing 1,3-difluorobenzene (X) by means of AlCl3 gives 4-(2,4-difluorobenzoyl)piperidine-1-carboxylic acid ethyl ester (XI), which is treated with concentrated HCl at 100 C to yield 4-(2,4-difluorobenzoyl)piperidine (XII). The condensation of piperidine (XII) with the 2-chloroethyl intermediate (V) by means of KI and NaHCO3 in refluxing acetonitrile affords the adduct (XIII), which is treated with hydroxylamine hydrochloride and KOH in refluxing pyridine/ethanol to provide the corresponding oxime (XIV). Finally, this compound is cyclized by means of KOH in refluxing water or with NaH in refluxing THF to afford in both cases the target 1,2-benzisoxazole.

1 Dalmases Barjoan, P.; Bosch Rovira, A.; Marquillas Olondriz, F.; Caldero Ges, J.M. (Vita-Invest, SA); Process for the preparation of 3-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)piperidino]ethyl]-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidine-4-one. ES 2050069 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(V) 23044 3-(2-chloroethyl)-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-one 63234-80-0 C11H15ClN2O 详情 详情
(VI) 17402 4-nipecotic acid;piperidine-4-carboxylic acid;p-nipecotic acid; Isonipecotic acid; Hexahydroisonicotinic acid; 4-Piperidinecarboxylic acid 498-94-2 C6H11NO2 详情 详情
(VII) 11229 1-[(Chlorocarbonyl)oxy]ethane;ethyl carbonochloridate; Carbonchloridic acid ethyl ester;Ethyl chloroformate;Ethyl chlorocarbonate 541-41-3 C3H5ClO2 详情 详情
(VIII) 50868 1-(ethoxycarbonyl)-4-piperidinecarboxylic acid C9H15NO4 详情 详情
(IX) 50869 ethyl 4-(chlorocarbonyl)-1-piperidinecarboxylate C9H14ClNO3 详情 详情
(X) 13095 m-Difluorobenzene; 1,3-Difluorobenzene 372-18-9 C6H4F2 详情 详情
(XI) 50870 ethyl 4-(2,4-difluorobenzoyl)-1-piperidinecarboxylate C15H17F2NO3 详情 详情
(XII) 23041 (2,4-difluorophenyl)(4-piperidinyl)methanone C12H13F2NO 详情 详情
(XIII) 50871 3-[2-[4-(2,4-difluorobenzoyl)-1-piperidinyl]ethyl]-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-one C23H27F2N3O2 详情 详情
(XIV) 50872 3-(2-[4-[(2,4-difluorophenyl)(hydroxyimino)methyl]-1-piperidinyl]ethyl)-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-one C23H28F2N4O2 详情 详情
Extended Information